Involvement of mitochondrial permeability transition in hepatitis B virus replication.

The HBx protein of human hepatitis B virus (HBV) activates a calcium-dependent kinase pathway which is essential for the viral replication. In this study, we found that HBx expression in the absence of other HBV proteins and in the context of HBV replication decreased the mitochondrial calcein-AM/CoCl(2) signals by 10% and 14% in HepG2 cells and by 15% and 10% in Huh7 cells, respectively. This indicates that HBx can induce mitochondrial permeability transition (MPT) and cause calcium effusion into the plasma. In addition, RNA interference of Cylophilin D decreased HBx-induced MPT and suppressed HBV DNA replication by 41% in HepG2 cells. Our results suggest that HBx expression can induce MPT and facilitate HBV DNA replication.